Pleiotropic trade-offs and compensatory adaptations. Trade offs between components of an organism's fitness are frequently invoked, although their generality is a matter of debate. Of particular significance are trade-offs between competitive ability and resistance to selective agents such as pesticides and parasites. If resistant organisms are competitively inferior to their sensitive counterparts, then the relative abundance of resistant organisms can be reduced by removing the selective agent. Two questions must be addressed to determine whether resistant organisms are, in fact, inferior competitors. Are there antagonistic pleiotropic effects of the genes conferring resistance on other components of fitness? Do these antagonistic effects persist, or are they eventually eliminated by compensatory adaptations? The bacterium Escherichia coli, its virus T4, and the antibiotic chloramphenicol will be used to examine pleiotropic trade-offs and compensatory adaptations. E. coli is ideal for this research because of its rapid evolution and potential for formal genetic analysis. Parallel experiments on chromosomal resistance to T4 and extrachormosomal resistance to chloramphenicol will proceed as follows: (i) select and geneticaly characterize resistant genotypes; (ii) compete sensitive and resistant genotypes to assay antagonistic pleiotropic effects; (iii) allow sensitive and reistant genotypes to evolve for many generations; (iv) compete evolved sensitive and resistant genotypes fo determine if compensatory adaptations have reduced antagonistic pleiotropic effects; and (v) identify the genetic basis of compensatory adaptations. Preliminary studies demonstrate both pleiotropic trade-offs and compensatory adaptations associated with resistance by E. coli to the virus T4.